Objective: To investigate the feasibility of peripheral sensory nerve stimulation combined with task-oriented training in patients with stroke during inpatient rehabilitation. Design: A pilot randomized crossover trial. Setting: Two rehabilitation hospitals. Subjects: Twenty-two patients with subacute stroke. Interventions: Participants were randomly assigned to two groups and underwent two weeks of training in addition to conventional inpatient rehabilitation. The immediate group underwent peripheral sensory nerve stimulation combined with task-oriented training in the first week, followed by another week with task-oriented training alone. The delayed group underwent the same training in reverse order. Main measures: Outcome measures were the level of fatigue and Wolf Motor Function Test. Patients were assessed at baseline, one and two weeks. Results: All participants completed the study with no adverse events. There was no significant difference in level of fatigue between each treatment. From baseline to one week, the immediate group showed larger improvements than the delayed groups in the Wolf Motor Function Test (decrease in mean time (± SD) from 41.9 ± 16.2 seconds to 30.6 ± 11.4 seconds versus from 46.8 ± 19.4 seconds to 42.9 ± 14.7 seconds, respectively) but the difference did not reach significance after Bonferroni correction ( P = 0.041). Within-group comparison showed significant improvements in the Wolf Motor Function Test mean time after the peripheral sensory nerve stimulation combined with task-oriented training periods in each group ( P < 0.01). Conclusion: Peripheral sensory nerve stimulation is feasible in clinical settings and may enhance the effects of task-oriented training in patients with subacute stroke.

T cells that are genetically engineered to express chimeric antigen receptor (CAR) have a strong potential to eliminate tumor cells, yet the CAR-T cells may also induce severe side effects due to an excessive immune response. Although optimization of the CAR structure is expected to improve the efficacy and toxicity of CAR-T cells, the relationship between CAR structure and CAR-T cell functions remains unclear. Here, we constructed second-generation CARs incorporating a signal transduction domain (STD) derived from CD3ζ and a 2nd STD derived from CD28, CD278, CD27, CD134, or CD137, and investigated the impact of the STD structure and signaling on CAR-T cell functions. Cytokine secretion of CAR-T cells was enhanced by 2nd STD signaling. T cells expressing CAR with CD278-STD or CD137-STD proliferated in an antigen-independent manner by their STD tonic signaling. CAR-T cells incorporating CD28-STD or CD278-STD between TMD and CD3ζ-STD showed higher cytotoxicity than first-generation CAR or second-generation CARs with other 2nd STDs. The potent cytotoxicity of these CAR-T cells was not affected by inhibiting the 2nd STD signals, but was eliminated by placing the STDs after the CD3ζ-STD. Our data highlighted that CAR activity was affected by STD structure as well as by 2nd STD signaling.

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Purpose] To investigate the effect of action observation therapy on the lower limb function of chronic stage hemiplegic stroke patients.[Subjects] The subjects were 21 chronic stage hemiplegic stroke patients.[Methods] The subjects were divided into an action observation therapy (AO) group, and a control group. The AO group watched a video of a person performing forward and lateral stepping for 5 min, then performed the same exercise themselves for 5 min. The control group performed only the forward and lateral stepping for 5 min. The outcome measures, the numbers of successful forward and lateral steps, the functional reach test (FRT), and the four square step test (FSST), were measured before, after, and 1 month after the intervention. [Result] In the comparison of the groups, mutual interaction was found for FRT. In the AO group, the successful number of forward steps, FRT, and FSST results showed significant improvements, which were maintained at 1 month post-intervention. Regarding the effective dose, all of the measured items of the AO group were better than those of the control group.[Conclusion] Action observation therapy for chronic stage hemiplegic stroke patients significantly improved lower limb performance in comparison with physical training alone.